Lien W H, Yeh T L, Yang Y K, Cherng C F G, Chen H H, Chen P S, Yu L
Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan 701, Taiwan, ROC.
Chin J Physiol. 2004 Mar 31;47(1):23-30.
Accrued evidence demonstrated the necessity of protein synthesis at acquisition, consolidation and expression stages in conditioning/learning tasks, while the underlying mechanisms of the maintenance of memory remained less explored. This study was designed to characterize the maintenance of methamphetamine-induced conditioned place preference, a drug-induced learning and memory. In addition, cycloheximide, a protein synthesis inhibitor, was used to examine the involvement of protein synthesis in the maintenance of such place preference memory. We found that the maintenance of the rapidly-established methamphetamine (2 mg/kg, i.p.) -induced conditioned place preference could be long-lasting and even over fifty days under the present protocol of extinction. Moreover, it was of interest to note the undulating expression of this conditioned place preference throughout the extinction protocol. Most importantly, as the methamphetamine-induced conditioned place preference was acquired and expressed by mice, the saline-pretreated control mice underwent numbers of intermittent extinction across a long-term retention test period, while cycloheximide-pretreated mice exhibited unaltered methamphetamine-induced conditioned place preference throughout the same retention test period. Taken together, we conclude that [1] methamphetamine-induced conditioned place preference could last for a long period of time, and such place preference memory is reluctant to extinguish even animals' repeated exposure to the previous conditioned environment at a drug-free status, and [2] blockade of protein synthesis may enhance the maintenance of the methamphetamine-induced conditioned place preference.
越来越多的证据表明，在条件反射/学习任务的获取、巩固和表达阶段，蛋白质合成是必要的，而记忆维持的潜在机制仍有待深入研究。本研究旨在表征甲基苯丙胺诱导的条件性位置偏爱（一种药物诱导的学习和记忆）的维持情况。此外，使用蛋白质合成抑制剂放线菌酮来检测蛋白质合成在这种位置偏爱记忆维持中的作用。我们发现，在当前的消退方案下，快速建立的甲基苯丙胺（2mg/kg，腹腔注射）诱导的条件性位置偏爱可以长期维持，甚至超过五十天。此外，值得注意的是，在整个消退方案中，这种条件性位置偏爱呈波动表达。最重要的是，当小鼠获得并表现出甲基苯丙胺诱导的条件性位置偏爱时，经生理盐水预处理的对照小鼠在长期保留测试期内经历了多次间歇性消退，而经放线菌酮预处理的小鼠在相同的保留测试期内甲基苯丙胺诱导的条件性位置偏爱未发生改变。综上所述，我们得出结论：[1]甲基苯丙胺诱导的条件性位置偏爱可以持续很长时间，并且即使动物在无药物状态下反复暴露于先前的条件环境中，这种位置偏爱记忆也难以消退；[2]蛋白质合成的阻断可能会增强甲基苯丙胺诱导的条件性位置偏爱的维持。
